POS0541 PREDICTORS OF REMISSION IN RHEUMATOID ARTHRITIS PATIENTS TREATED WITH UPADACITINIB OR ADALIMUMAB IN THE SELECT-COMPARE PHASE 3 STUDY: CLINICAL STATUS AT WEEK 12, BUT NOT STANDARD LABORATORY MEASURES, PROVIDES THE BEST CURRENT PREDICTOR OF REMISSION AT WEEK 26
Authors: T. Sornasse, F. Cai, F. Hong, S. Anyanwu, I. H. Song, M. Bukhari
Journal: Annals of the Rheumatic Diseases (2022)

Background Upadacitinib (UPA, 15 mg QD), an oral JAK1 selective inhibitor, showed greater efficacy compared to adalimumab (ADA, 40 mg EOW) at week 12 in patients with active rheumatoid arthritis (RA) on background methotrexate (MTX) in the SELECT-COMPARE phase 3 study 1 . Treatment with UPA compared to ADA resulted in a larger proportion of patients reaching CDAI Remission (REM) at week 26 (23% vs. 14%, p-value ≤ 0.001). Because remission is the goal in managing RA, it is of clinical relevance to identify early during the treatment course who might be able to achieve this state. It has been reported that early response to therapy with UPA was associated with achieving CDAI REM at week 26 2 . In parallel, it has been reported that reduction in monocyte can predict DAS28-ESR REM in RA patients treated with anti-TNF therapy 3 . However, the relative predictive values of clinical and standard laboratory measures have not been compared side-by-side. Objectives To determine post-hoc the relative predictive values of selected clinical and standard laboratory measures collected at week 12 for identifying RA patients who will be in CDAI REM at week 26 upon treatment with UPA or ADA. Methods Clinical (CDAI, SDAI, and DAS28-CRP) and laboratory data (CRP, ESR, CBC with differential, and Lipids) for all available patients enrolled in the SELECT-COMPARE phase 3 study were included in this post-hoc analysis (UPA: n =623 [CDAI REM at wk26 = 23.8%]; ADA: n = 316 [CDAI REM at wk 26 = 14.2%]). Patients who switched treatment between weeks 14 and 22 due to not reaching at least 20% improvement in tender and swollen joints were classified as non-responders for CDAI REM at week 26. The predictive value of clinical and laboratory endpoints recorded at week 12 for determining CDAI REM status at week 26 was assessed by univariate logistic regression. We report the performance of each model as ROC AUC with a cutoff of 0.75 for meaningful predictive value. Results For both patients treated with UPA and those treated with ADA, clinical disease activity status measures (CDAI, SDAI, and DAS28-CRP) and relative change in disease activity measures (Percent Change [PCHG] in CDAI, PCHG in DAS28-CRP, and PCHG in SDAI) at week 12 resulted in the highest predictive performance for determining CDAI REM status at week 26 (Figure 1). In contrast, none of the selected standard laboratory measures (CRP, ESR, CBC with differential, and Lipids) reached a meaningful predictive value (ROC AUC &lt; 0.75). Of note, cell numbers and changes in cell numbers (including Neutrophils Lymphocytes, Basophils, Eosinophils, and Monocytes) at week 12 had no meaningful predictive value for determining CDAI REM at week 26. Figure 1. Univariate Logistic Models to Predict CDAI REM at Week 26 in Active RA Patients who had an Inadequate Response to MTX: ROC Analysis AUC. Legend : All evaluated parameters were recorded at Week 12; CHG = Change from Baseline to Week 12; PCHG = Percent Change from Baseline to Week 12 Conclusion This analysis suggests that standard laboratory measures (CRP, ESR, CBC with differential, and Cholesterol) at week 12 do not represent useful predictors for REM at week 26 in csDMARD-IR RA patients. In particular, blood cell numbers and the changes in these measures at week 12 do not provide additional predictive value in our analyses, contrasting with the results from Amarnani and colleagues 3 . Hence, clinical disease activity levels and changes in these measures at week 12 remain adequate predictors of CDAI REM at week 26. Still, the absolute predictive performance of clinical measures remains suboptimal, highlighting the need to dedicate continued efforts to identify and validate improved predictors of long-term REM in RA. References [1]Fleischmann, R. et al. Arth Rheumatol 71 , 1788-1800 (2019). [2]Kavanaugh, A. et al. J Clin Rheumatol 27 , S81-S81 (2021). [3]Amarnani, R. et al. Ann Rheum Dis 80 , 448-449 (2021). Acknowledgements AbbVie, Inc was the study sponsor, contributed to the study design, data collection, analysis &amp; interpretation, and writing, reviewing, and approval of the final version. Disclosure of Interests Thierry Sornasse Shareholder of: AbbVie, Employee of: AbbVie, Fang Cai Shareholder of: AbbVie, Employee of: AbbVie, Feng Hong Shareholder of: AbbVie, Employee of: AbbVie, Samuel Anyanwu Shareholder of: AbbVie, Employee of: AbbVie, In-Ho Song Shareholder of: AbbVie, Employee of: AbbVie, Marwan Bukhari Speakers bureau: Bristol-Myers Squib, UCB celltech, Roche/Chugai, Pfizer, Abbvie, Merck, Mennarini, Sanofi-aventis, Eli-Lilly, Janssen, Amgen, Novartis and Gilead, Paid instructor for: honoraria from educational groups revalidaid and TREG consultants.